Chemical models of oxidative phosphorylation

Chemical models for coupling oxidation to phosphorylation are summarized and examined both from the standpoint of organic reaction mechanisms and with respect to their relevance to mitochondria and chloroplasts. In order to accelerate the progress of our research in bioenergetics, it is suggested to focus at least as much attention on structural biochemistry as on phenomenological observations of energy-transducing membranes.Supported in part by Public Health Service Research Grant No. GM 19990 from the National Institute of General Medical Sciences and by National Science Foundation Research Grant No. PCM 74-24083 A01     

Thymidine kinase activity and human chromosome No. 18

Somatic cell hybridization studies have suggested that the locus for human thymidine kinase is on a No. 17 or No. 18 chromosome. To evaluate further this possibility, fibroblast cell cultures from patients with partial monosomy 18 and trisomy 18 were assayed for thymidine kinase activity; the enzyme levels in these cell extracts were normal. If the enzyme activities reflect a simple gene dose effect, these results suggest that the human thymidine kinase locus is not situated on the No. 18 chromosome.Supported in part by Grant # MR 0504A-69 from the Division of Mental Retardation, Social and Rehabilitation Service, Department of Health, Education and Welfare, and by the Institute of Child Health and Human Development, Grant # DO 4612, Mental Retardation Research Center, UCLA/NPI.     

Effect of atrazine in combination with captan or thiram upon fungal and bacterial populations in the soil

Pesticides were added to soil at a rate of 10 mg/kg and then planted with corn, wheat, or bean seeds. Captan and thiram caused an initial decrease in the fungal populations but by 108 days the populations returned to levels found in untreated soils. The bacterial populations fluctuated inversely with the fungal populations. In soil planted with corn, atrazine had no effect on the microbial populations, however, in soil containing wheat and beans, populations of fungi and bacteria increased. Stimulation of the microbial populations in the atrazine-treated soils was attributed to the decay of the dead wheat and bean plants. Atrazine in combination with captan or thiram had neither synergistic nor antagonistic effects on the microbial populations. This study was supported by Public Health Service Research Grant No. CC 00284, from the National Communicable Disease Center, Atlanta, Georgia. This study was supported by Public Health Service Research Grant No. CC 00284, from the National Communicable Disease Center, Atlanta, Georgia.     

Isozyme variability in species of the genus Drosophila. I. A multiple allelic isozyme system in Drosophila busckii: Inheritance and general considerations

Starch gel electrophoretic analysis of a triallelic leucine aminopeptidase polymorphism in a laboratory population of Drosophila busckii is described. The three alleles involved are expressed without dominance. A series of single-pair matings revealed an excess of heterozygous types in most segregating families, suggesting selection against the homozygous genotypes. A few cases of heterogeneity among progeny extracted from a single family were the result of matings that produced Mendelian ratios. These few cases had no clear genetic explanation, but there is a suggestion of two isoalleles for the electrophoretically intermediate enzyme.The research reported here was begun at the University of Hawaii and completed at the University of Texas and was supported (in part) by Public Health Service Research Grant No. GM 11609 to W. S. Stone and M. R. Wheeler and by Training Grant No. 2 T1-GM-337-06 and GM 00337-07 to R. P. Wagner et al., from the National Institutes of Health.     

C. parvum in germ-free mice

Summary The effect of previous sensitization to C. parvum, by cross-reacting antigens from other bacteria, on the immunostimulatory effects of C. parvum treatment were studied in germ-free and conventional mice. It was found that the development of splenomegaly and specific delayed hypersensitivity following C. parvum injection were similar in both germ-free mice and conventional mice.Supported by U.S. Public Health Service Grant No. 5S07 RR05705 and NIH Grant no. AM 18530Visiting Investigator. Present address: Department of Experimental Immunobiology, The wellcome Research Laboratories Beckenham, Kent, England.Recipient of a post-doctoral fellowship from the National Foundation for Ileitis and Colitis Inc.Recipient of Research Career Development Award No. AM 0073 from the National Institute of Arthritis, Metabolism and Digestive Diseases     

Familial DiGeorge syndrome and associated partial monosomy of chromosome 22

Summary Partial monosomy of 22q due to an unbalanced 4;22 translocation was seen in a 2-month-old male with Type I truncus arterious, dysmorphic features, and T-cell abnormalities. The family history revealed a previous sib with Type I truncus arteriosus, thymic aplasia, and parathyroid hypoplasia noted on postmortem examination, consistent with DiGeorge syndrome. Evaluation of the asymptomatic mother of these two patients revealed partial T-cell deficiency and the same unbalanced translocation with deletion of proximal 22qll. These findings provide further evidence that some cases of complete or partial DiGeorge syndrome are associated with monosomy of the proximal long arm of chromosome 22, and they may explain many, if not all, familial cases of the syndrome.Supported in part by National Foundation-March of Dimes Grant No. 2-161/C-331. Funds from the Texas Department of Health through PL94-278 National Genetic Diseases Act, from the Robert J. Kleberg, Jr. Center for Human Genetics, and USPHS Grant No. RR-05425.     

Congenital diaphragmatic hernia, kidney agenesis and cardiac defects associated with Slit3-deficiency in mice

Slit3 along with Slit1 and Slit2 comprise the Slit family of proteins. The latter two proteins are known to be involved in axon guidance and cell migration during animal development. However, little is know about the functions of Slit3. We created a Slit3-deficient mouse model from an OmniBank ES cell line with a Slit3 allele trapped by insertional mutagenesis to analyze the in vivo functions of this protein. In this model, congenital diaphragmatic hernia is the most obvious phenotype. Herniation was found to be caused by a defective central tendon (CT) of the diaphragm that remained fused with the liver. Electron microscopic analyses of the defective CT revealed disorganized collagen fibrils that failed to form tight collagen bundles. The hearts of Slit3-deficient mice have an enlarged right ventricle. In addition, 20% of homozygous mice also showed a range of kidney defects that include unilateral or bilateral agenesis of the kidney and ureter, or varying degrees of renal hypoplasia. Thus, we concluded that Slit3 is involved in the development of multiple organ systems that include the diaphragm and the kidney. Slit3-deficient mice represent a genetic animal model for physiological and pathological studies of congenital diaphragmatic hernia.     

Theory of hemoglobin facilitated oxygen transport

The transport of oxygen in a hemoglobin-saturated medium is theoretically investigated using classical transport theory. It is found that all the chemical complexes can be expressed as a single function of oxygen pressure. A potential difference together with apH shift is predicted to occur across the medium. This research was supported by the United States Public Health Service Training Grant No. 5-T1-GM-833 from the National Institute of General Medical Sciences. This research was supported by a United States Public Health Service Research Career Program Award 5-K6-GM-18,420 from the National Institute of General Medical Sciences.     

An avoidance learning situation. A neural net model

A simple avoidance situation is considered in terms of a neural net learning model. Data for the control situation can be represented by an expression having three parameters which determine the initial and the steady state activities together with the transient aspects. The introduction of a learning parameter then allows one to calculate satisfactorily the results obtained in the experimental situation in which shock is applied. This research was supported in part by the United States Air Force through the Air Force Office of Scientific Research of the Air Research Development Command under Grant No. AF AFOSR 370-63 and in part by the United States Public Health Service Grant RCA GM K6 18,420.     

Lesch-Nyhan syndrome: Absence of the mutant enzyme in erythrocytes of a heterozygote for both normal and mutant hypoxanthine-guanine phosphoribosyl transferase

Subjects heterozygous for the Lesch-Nyhan syndrome with a deficiency of the X-linked gene for the enzyme hypoxanthine-guanine phosphoribosyl transferase (PRT) would be expected to have two populations of erythrocytes in roughly equal proportions—one type with the normal enzyme and the other type exhibiting the mutant form of the enzyme. In contrast to this prediction, previous studies utilizing an X-linked gene for another enzyme as a marker for the PRT locus have suggested that erythrocytes from heterozygotes consist largely of cells with the normal form of the enzyme. We have recently described a mutant form of hypoxanthine-guanine phosphoribosyl tranferase with altered kinetic properties which allow it to be measured in artificial mixtures with the normal enzyme. The mutant enzyme could not be detected in erythrocyte lysates from a proven heterozygote for both the normal and this mutant form of the enzyme. This provides additional evidence that either inactivation of the X-chromosome in erythropoietic tissue from the heterozygote for PRT deficiency is not random or that random X-chromosome inactivation is followed by selection against erythrocyte precursors with the mutant enzyme.This study was supported in part by USPHS Research Grant No. AM14362, USPHS Training Grant No. AM05620, and a grant (RR-30) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health.     

Theory for the number of genes affecting quantitative characters

Summary A general expression for gene number estimation which encompasses the conventional formula was derived. It provides a basis for gene number estimation from the data of recurrent selection experiments that are not of sufficient duration to measure total response to selection.Gene number estimates are considerably more reliable when heritability is high. The effect of heritability on sampling variance is particularly important when gene number is large.Generally the most effective ways of decreasing the variance of a gene number estimate will be 1) to increase the number of generations in a primary selection program, 2) to increase the number of generations in the two way selection program and 3) to increase population size.From a thesis submitted by the author in partial fulfillment of the requirements for the Ph.D. degree. Received March, 1975. Work supported by Public Health Service Grant GM 16074, by the Minnesota Agricultural Experiment Station and by National Institutes of Environmental Health Sciences Grant No. 5T32 ES07011-02.Former Research Assistant, Genetics and Cell Biology, University of Minnesota; Currently Post-doctoral Fellow in Environmental Health Measurement and Statistics.     

Anhidrotic ectodermal dysplasia as autosomal recessive trait in an inbred kindred

Anhidrotic ectodermal dysplasia in an inbred kindred was observed in three sisters and three first cousins. This was interpreted as presumptive evidence for autosomal recessive inheritance and it is suggested that in addition to its known genes, anhidrotic ectodermal dysplasia occasionally may be caused by an autosomal recessive gene.This investigation was supported by Public Health Service Research Grant No. FR 00123, from GCRC-DRFR and by a Fellowship in Pediatric Teratology of the Children's Hospital Research Foundation, Cincinnati.     

Acid phosphatase in the Golgi apparatus of cells forming extracellular matrix of hard tissues

Summary Histochemical studies using cryostat sections of fixed rodent fetal and newborn tissues indicated that acid phosphatase (APase) staining of the Golgi apparatus (GA) of cells secreting matrix for hard tissue formation was a general phenomenon. The enzyme was chiefly observed in the GA of tall secretory ameloblasts involved in enamel formation and in the GA of odontoblasts forming dentine; lysosome-like granules reactive for this enzyme were also observed in these cells. Activity was also intense in the GA and lysosomes of osteoblasts involved in intramembranous and endochondral bone formation.High levels of APase in the GA of extracellular matrix-forming cells appeared to correlate with secretory activity. The GA of most other cells, even chondroblasts forming cartilage matrix, had much less marked APase activity. Contrary to previous suggestions, it appears that APase may have a more direct role in osteogenesis than the osteolytic or resorptive action usually cited.This investigation was supported by PHS Research Grant No. DE 02668 from the National Institute of Dental Research and in part by General Research Support Grant No. RR 5333 from the General Research Support Branch of the National Institutes of Health.The authors gratefully acknowledge the excellent technical assistance of Dorothy H. Clapp and Peggy E. Yates.     

21 ring chromosome in a girl with stigmata of Down's and G deletion I syndromes

Summary An 11-year-old girl with severe psychomotor retardation and other congenital anomalies characteristic of Down's and G deletion I syndromes, was confirmed to be a chromosome 21 ring carrier by R- and G-banding techniques. The dynamics of the ring evolution resulting in a population of complex unstable rings, as in our index case, and the effects of the consequent ring mosaicism are briefly discussed.This work was supported in part by Grant No. 500.6/1143 of the Public Health Ministry.     

The relationship between nerves and smooth muscle cells in the rat iris

Summary The sphincter muscle in the rat iris forms irregular strands in the stroma. Bundles of unmyelinated axons run among the muscle cells. After sympathetic denervation some axons degenerate. This should indicate that sympathetic and parasympathetic nerves are present in the same nerve net. The parasympathetic axons possess varicosities, that is, enlargements containing mitochondria and synaptic vesicles. These varicosities show a similar structural relationship to the muscle cells as do the varicosities of sympathetic nerves. No obvious ultrastructural difference is observed between the sympathetic and parasympathetic varicosities.This study has been supported by research grants (U267 and Y247) from the Swedish Medical Research Council and by a Public Health Service Research Grant (NB05236-01) from the National Institute of Neurological Diseases and Blindness.     

A neural net model for escape learning

An escape learning situation is discussed in terms of a neural model in which a stimulus can result in a conditioned excitement and a specific conditioned response. By using the simplest relations between the strengths of conditioning and the number of reinforcements and by introducing a distribution of fluctuations occurring regularly in time, one can calculate the probabilities of various responses, as well as the various latencies, in successive trials. The results are in moderately satisfactory agreement with the data of R. L. Solomon and L. C. Wynne (Psychol. Monogr.,67, No. 4, 1953). Consequences of the model for various experimental situations are discussed. This research was supported in part by the United States Public Health Service Grant RCA GM K6 18,420 and in part by the United States Air Force through the Air Force Office of Scientific Research of the Air Research Development Command under Grant No. AF AFOSR 370-64.     

Social interactions of monkeys reared in a nuclear family environment versus monkeys reared with mothers and peers

Four-year-old laboratory-born rhesus monkeys that had been reared in a nuclear family social environment consisting of mothers, fathers, siblings, peers, and other adults of both sexes were permitted to interact in various combinations with equal-aged monkeys that had been reared in an environment consisting of only mothers and peers. It was found that in most interaction sessions nuclear family subjects exhibited significantly higher levels of dominance and activity behaviors and significantly lower levels of submissive and passive behaviors than the mother-peer-reared subjects. These differences were not evident when subjects were tested within their own rearing groups. The significance of the results with respect to previous and future studies of social development in differential social environments is discussed.This research was supported by grant No. MH-11894 from the National Institute of Mental Health to the University of Wisconsin Primate Laboratory, by the Grant Foundation, and by grant No. RR-0167 from the National Institutes of Health to the University of Wisconsin Primate Research Center.     

On visual adaptation: I. Photochemistry

Quantitative aspects of the photochemistry of visual adaptation are considered. A simplied model is given that fits data on changes of rhodopsin concentration during and following strong illumination. A variation on Wald’s compartment hypothesis is shown to fit the quasilinear dependence of log threshold upon pigment concentration. Finally, there is a brief review of pertinent data on cone pigments. This research was supported in part by the United States Air Force through the Air Force Office of Scientific Research of the Air Research Development Command under Contract No. AF(638)-414, and in part by the United States Public Health Service Training Grant 2G-833.     

Methods for the study ofin vitro immunization of mouse spleen cells

Conclusion We have reviewed some of our experiences in developing techniques for studying the functions of the cells of the immune system. It is quite clear that much remains to be done. Improvements in the culture system are needed to permit cells to be grown for longer durations and at lower cell concentrations. The important effects of fetal calf serum should be defined. More sophisticated methods for separating cells into distinct functional populations must be developed. New assays for identifying other functions of the cells, particularly a method for directly assaying the number of precursor cells in a population, are needed. When these techniques are applied to the study of immune cells, further facts should be learned which will permit the development of significant, testable hypotheses on the function and relationships of the cells of the immune system. This is publication No. 298 from the Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California 92037. This work was supported in part by U.S.P.H.S. Grant 7007 and in part by American Cancer Society Grant E-395. Dr. Mishell is supported by American Cancer Society Grant E-395. Dr. Dutton is supported by a Dernham Fellowship of the California Division, American Cancer Society (No. D-100). Dr. Raidt is supported by United States Public Health Service Postdoctoral Fellowship No. 7-F2-A1-31,590.